The use of AFP and DCP as serum biomarkers to differentiate between hepatocellular carcinoma and intrahepatic cholangiocarcinoma in non-cirrhotic livers.

e15162 Background: Differential diagnosis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) can be challenging in patients without evidence of liver cirrhosis. Definitive diagnosis is based on tissue biopsy. We investigated if the use of serum biomarkers could help differentiate between these two types of malignancies, thereby avoiding the risks associated with biopsy. Methods: Patients with cholangiocarcinoma and HCC were recruited from Queen Elizabeth Hospital, Birmingham, UK; blood samples were collected at time of diagnosis. Two biomarkers, alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) were measured in the serum samples from 56 patients with cholangiocarcinoma and 35 patients with HCC without evidence of liver cirrhosis. Of the 56 patients with cholangiocarcinoma, 17 were intrahepatic and 39 were extrahepatic. Results: 17 ICC and 35 HCC were included in the analysis. The levels of AFP and DCP were much higher in HCC as compared to ICC. The median AFP was 64.6 (IQR 10.9, 3564.2) in HCC as compared to 3 (IQR 2.4, 3.9) in ICC. Similarly, the median DCP was 215.41 (IQR 22.46, 692.53) in HCC as compared to 0.33 (IQR 0.16, 1.08) in ICC. Stepwise logistic regression was performed using both biomarkers. Log- DCP remained significant at 95% level in predicting HCC from ICC, giving an AUC of 0.96. Conclusions: In patients with a non-cirrhotic liver and radiological evidence of cancer, measurement of serum AFP and DCP level may help differentiate between HCC and ICC. In this study, DCP is the most useful discriminator between HCC and ICC. Further prospective studies should be done with larger sample sizes to validate the use of AFP and DCP as diagnostic biomarkers in this clinical setting.

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DIAGNOSTIC PERFORMANCE OF PIVKAII AND NEW POTENTIAL SERUM BIOMARKERS GP3, CSTB, SCCA1 AND HGF FOR DIAGNOSIS OF HEPATOCELLULAR CARCINOMA IN PATIENTS WITH ALCOHOLIC LIVER CIRRHOSIS

10.26226/morressier.57c5383fd462b80296c9c970 ◽

2016 ◽

Author(s):

Ivica Grgurevic

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Diagnostic Performance ◽

Serum Biomarkers ◽

Alcoholic Liver Cirrhosis

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The APAC Score: A Novel and Highly Performant Serological Tool for Early Diagnosis of Hepatocellular Carcinoma in Patients with Liver Cirrhosis

Journal of Clinical Medicine ◽

10.3390/jcm10153392 ◽

2021 ◽

Vol 10 (15) ◽

pp. 3392

Author(s):

Joeri Lambrecht ◽

Mustafa Porsch-Özçürümez ◽

Jan Best ◽

Fabian Jost-Brinkmann ◽

Christoph Roderburg ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

At Risk ◽

Liver Cirrhosis ◽

Early Stage ◽

Treatment Options ◽

Growth Factor Receptor ◽

Serum Samples ◽

Disease Etiology ◽

Risk Patients ◽

Scoring Tool

(1) Background: Surveillance of at-risk patients for hepatocellular carcinoma (HCC) is highly necessary, as curative treatment options are only feasible in early disease stages. However, to date, screening of patients with liver cirrhosis for HCC mostly relies on suboptimal ultrasound-mediated evaluation and α-fetoprotein (AFP) measurement. Therefore, we sought to develop a novel and blood-based scoring tool for the identification of early-stage HCC. (2) Methods: Serum samples from 267 patients with liver cirrhosis, including 122 patients with HCC and 145 without, were collected. Expression levels of soluble platelet-derived growth factor receptor beta (sPDGFRβ) and routine clinical parameters were evaluated, and then utilized in logistic regression analysis. (3) Results: We developed a novel serological scoring tool, the APAC score, consisting of the parameters age, sPDGFRβ, AFP, and creatinine, which identified patients with HCC in a cirrhotic population with an AUC of 0.9503, which was significantly better than the GALAD score (AUC: 0.9000, p = 0.0031). Moreover, the diagnostic accuracy of the APAC score was independent of disease etiology, including alcohol (AUC: 0.9317), viral infection (AUC: 0.9561), and NAFLD (AUC: 0.9545). For the detection of patients with (very) early (BCLC 0/A) HCC stage or within Milan criteria, the APAC score achieved an AUC of 0.9317 (sensitivity: 85.2%, specificity: 89.2%) and 0.9488 (sensitivity: 91.1%, specificity 85.3%), respectively. (4) Conclusions: The APAC score is a novel and highly accurate serological tool for the identification of HCC, especially for early stages. It is superior to the currently proposed blood-based algorithms, and has the potential to improve surveillance of the at-risk population.

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Surveillance for Hepatocellular Carcinoma Also Improves Survival of Incidentally Detected Intrahepatic Cholangiocarcinoma Arisen in Liver Cirrhosis

Liver Cancer ◽

10.1159/000509059 ◽

2020 ◽

Vol 9 (6) ◽

pp. 744-755

Author(s):

Francesco Tovoli ◽

Pietro Guerra ◽

Massimo Iavarone ◽

Letizia Veronese ◽

Matteo Renzulli ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Liver Cirrhosis ◽

Propensity Score ◽

Intrahepatic Cholangiocarcinoma ◽

Lead Time ◽

Propensity Score Analysis ◽

Lead Time Bias ◽

Cirrhotic Patients ◽

Surgical Treatments

Background: Due to its poor survival, intrahepatic cholangiocarcinoma (ICC) is held to be a much more aggressive cancer than hepatocellular carcinoma (HCC). In most published series, patients were diagnosed when symptomatic. However, ICC is now increasingly being discovered during the surveillance for HCC in cirrhosis. Whether this earlier detection of ICC is associated with an equally dismal prognosis or not is unknown. Methods: This is amulticenter retrospective study of consecutive ICC patients. Patients were stratified into subgroups according to the absence/presence of cirrhosis. A propensity score matching was performed to reduce the potential biases. Cirrhotic patients were further stratified according to their surveillance status. The lead-time bias and its potential effects were also estimated. Results: We gathered 184 patients. Eighty-five patients (46.2%) were cirrhotic. Liver cirrhosis was not related to a worse overall survival (33.0 vs. 32.0 months, p = 0.800) even after the propensity score analysis (43.0 in vs. 44.0 months in 54 pairs of patients, p = 0.878). Among the cirrhotic population, 47 (55.3%) patients had received a diagnosis of ICC during a surveillance programme. The 2 subgroups differed in maximum tumour dimensions (30 vs. 48 mm in surveyed and non-surveyed patients, respectively). Surveyed patients were more likely to receive surgical treatments (59.8 vs. 28.9%, p = 0.003). Overall survival was higher in surveyed patients (51.0 vs. 21.0 months, p < 0.001). These benefits were confirmed after correcting for the lead-time bias. Conclusions: Cirrhotic patients have different clinical presentation and outcomes of ICC according to their surveillance status. In our series, ICC in cirrhosis was not associated with worse OS. Cirrhosis itself should not discourage either surgical or non-surgical treatments.

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Identification of Protein Expression Changes in Hepatocellular Carcinoma through iTRAQ

Disease Markers ◽

10.1155/2020/2632716 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Yuanyuan Zhang ◽

Xia Ying ◽

Qian Zhao ◽

Jinlu Ma ◽

Dan Zhang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Serum Levels ◽

Serum Biomarkers ◽

The Cancer Genome Atlas ◽

Paraoxonase 1 ◽

Serum Samples ◽

Absolute Quantitation ◽

Isobaric Tags ◽

Tcga Dataset ◽

Normal Controls

Background. Hepatocellular carcinoma (HCC) is a malignant tumor associated with a poor prognosis. Serum biomarkers of HCC have the potential to improve the diagnosis, provide a means to monitor the tumors, and predict their malignancy. Proteins that are expressed differentially between HCC patients and normal controls have the potential to be biomarkers. Method. Serum samples from 10 confirmed HCC patients and 10 controls were collected. The differentially expressed proteins in the serum were identified using an isobaric tags for relative and absolute quantitation- (iTRAQ-) based method. Potential serum biomarkers were validated by ELISA in another 20 HCC patients and 20 controls. Their expression data in HCC were extracted from The Cancer Genome Atlas (TCGA) dataset. Results. A total of 260 proteins were measured in the serum of HCC patients and compared to those in sex- and age-matched normal controls. Forty-one proteins displayed significant changes, with 26 being downregulated and 15 being upregulated. Upregulated proteins included alpha-1-antitrypsin (A1AT) and peroxiredoxin 2 (PRDX2), and downregulated proteins included paraoxonase 1 (PON1) and C-reactive protein (CRP). We then used ELISA to measure serum levels of A1AT, PRDX2, PON1, and CRP in another 20 patients with HCC and found that only PON1 levels were consistent with the iTRAQ result. In TCGA dataset, PON1 expression was downregulated in HCC tissues (P<0.001) and low expression of PON1 was associated with poor survival in HCC patients (P<0.001). Conclusions. PON1 could act as a biomarker for HCC to assist in the diagnosis of HCC.

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Abundance of Immunologically Active Alanine Aminotransferase in Sera of Liver Cirrhosis and Hepatocellular Carcinoma Patients

Clinical Chemistry ◽

10.1373/clinchem.2008.102996 ◽

2009 ◽

Vol 55 (5) ◽

pp. 1022-1025 ◽

Cited By ~ 8

Author(s):

Hyun Jeong Kim ◽

Sang Wook Oh ◽

Dong Joon Kim ◽

Eui Yul Choi

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Liver Disease ◽

Enzymatic Activity ◽

Enzyme Immunoassay ◽

Roc Curve ◽

Alanine Aminotransferase ◽

Liver Diseases ◽

Serum Samples ◽

Sandwich Enzyme Immunoassay

Abstract Background: Although alanine aminotransferase (ALT) is a widely used indicator of liver function, ALT enzymatic activity may not always reflect the degree of liver damage. Improved methods or approaches would be useful. Methods: Monoclonal antibodies (mAbs) to ALT were generated to develop a sandwich enzyme immunoassay system. We used an immunoassay to measure ALT mass concentration and a common biochemical analyzer to assay ALT enzymatic activity in serum samples from patients with liver diseases and healthy individuals. The results from the 2 methods were compared and analyzed by ROC curve analysis. Results: The ALT sandwich enzyme immunoassay system demonstrated reliable performance in linearity, recovery, and imprecision studies. The ALT activity assay exhibited a higher diagnostic accuracy in acute hepatitis (AH) patients, but the ALT immunoassay exhibited higher sensitivity and specificity in patients with chronic liver diseases. The areas under the ROC curve for ALT mass and enzymatic activity were 0.82 and 0.98, respectively, in AH, 0.99 and 0.52 in hepatocellular carcinoma (HCC), and 0.94 and 0.45 in liver cirrhosis (LC). Serum samples from HCC and LC patients had higher amounts of ALT–immunoglobulin complexes [median A450, 1.7 (interquartile range, 1.4–1.9)] than the other groups [1.3 (interquartile range, 0.9–1.6)]. Conclusions: Our analysis of sera from the HCC and LC patient groups revealed considerable amounts of immunologically active but catalytically inactive ALT. The amount of the ALT–immunoglobulin complex increased with the severity of the liver disease. The 2-site immunoassay method may be useful in the differential diagnosis of some causes of liver disease.

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LC/MS-Based Global Metabolomic Identification of Serum Biomarkers Differentiating Hepatocellular Carcinoma from Chronic Hepatitis B and Liver Cirrhosis

ACS Omega ◽

10.1021/acsomega.0c04259 ◽

2021 ◽

Author(s):

Hong Y. Pan ◽

Qing Q. Wu ◽

Qiao Q. Yin ◽

Yi N. Dai ◽

Yi C. Huang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Serum Biomarkers

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Identification of serum biomarkers associated with hepatitis B virus-related hepatocellular carcinoma and liver cirrhosis using mass-spectrometry-based metabolomics

Metabolomics ◽

10.1007/s11306-015-0804-9 ◽

2015 ◽

Vol 11 (6) ◽

pp. 1526-1538 ◽

Cited By ~ 15

Author(s):

Yonghai Lu ◽

Chong Huang ◽

Liang Gao ◽

Yong-Jiang Xu ◽

Sin Eng Chia ◽

...

Keyword(s):

Mass Spectrometry ◽

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Serum Biomarkers ◽

B Virus

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NMR and LC/MS-based global metabolomics to identify serum biomarkers differentiating hepatocellular carcinoma from liver cirrhosis

International Journal of Cancer ◽

10.1002/ijc.28706 ◽

2014 ◽

Vol 135 (3) ◽

pp. 658-668 ◽

Cited By ~ 66

Author(s):

Yue Liu ◽

Zhanying Hong ◽

Guangguo Tan ◽

Xin Dong ◽

Genjin Yang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Serum Biomarkers ◽

Global Metabolomics

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Vitamin D Receptor Gene Polymorphisms and the Risk of Chronic Hepatitis C Related Hepatocellular Carcinoma in Egyptian Population

The Open Biomarkers Journal ◽

10.2174/1875318302111010079 ◽

2021 ◽

Vol 11 (1) ◽

pp. 79-85

Author(s):

Amal A. Mohamed ◽

Sherief Abd-Elsalam ◽

Hanan M. Mostafa ◽

Asmaa Abdalla ◽

Ahmed Farouk ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Vitamin D ◽

Liver Cirrhosis ◽

Hepatitis C ◽

Vitamin D Receptor ◽

Gene Polymorphisms ◽

Receptor Gene ◽

Stepwise Logistic Regression ◽

Vitamin D Receptor Gene ◽

Egyptian Patients

Background: Small percentage of hepatitis C (HCV) patients develop hepatocellular carcinoma (HCC) during their lifetime, suggesting that genetic factors might modulate HCC development. Numerous variations on the vitamin D receptor gene (VDR) have been recognized in human cancers. The majority of them cause VDR to be unable to bind to 1, 25-OH-D. The aim of the present work was to investigate the relation of VDR FokI (rs2228570), BsmI (rs3782905) and ApaI (rs7975232) gene polymorphisms and the risk of HCC development in chronic HCV Egyptian patients. Methods: A total of 311 Egyptian patients were enrolled for this study. They were divided into 3 groups: 103 patients with liver Cirrhosis, 107 patients with HCC and 101 normal healthy subjects as the control group. Human genomic DNA Extraction was carried out using QIAamp® DNA Blood Mini Kit (QIAGEN) Genotyping of VDR ApaI (rs7975232) single nucleotide polymorphism (SNP) was carried out using real-time PCR TaqMan allelic discrimination assay with allele-specific designed fluorescent MGB probes. Results: Patients with HCC had a higher frequency of ApaI CC genotype (P=0.035) CI (0.031-0.038). Patients with HCC carried a higher ratio of ApaI CC genotype compared to those with liver cirrhosis (x2=5.4 and P = 0.03) or controls (x2=6.8 and P = 0.01). Univariate analysis revealed that age, lower platelet count (<150×103/μL), higher AFP (>100 ng/ml), and ApaI CC genotype were the factors significantly associated with the development of HCC. Stepwise logistic regression analysis showed that all were independent predictors. Conclusion: ApaI CC VDR gene mutation is an independent risk factor for HCC development in Egyptian Cirrhotic HCV patients.

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